Our long-term objective is to understand how airway epithelial cell micro-RNAs (miRNAs) function and determine how these miRNAs contribute to asthma. Ciliated and secretory cells within the airway epithelium establish and maintain a protective barrier. Changes in epithelial cell function are a consistent feature of asthma and contribute to airway obstruction, morbidity, and mortality. Exciting recent advances demonstrate that miRNAs regulate expression of many genes and that miRNAs play major roles in development and disease. However, the contributions of miRNAs to airway epithelial cell differentiation and function and the roles of these miRNAs in asthma remain unknown. Our preliminary data demonstrate that miRNA expression changes dramatically during airway epithelial cell differentiation, and that there are significant differences in miRNA expression between asthmatic and healthy subjects. We propose to develop approaches for measuring and manipulating miRNA levels and activities in airway epithelial cells. We will use these approaches to study how selected miRNAs identified in the preliminary studies affect airway epithelial cell differentiation and gene expression. Results of these R21-funded studies will set the stage for subsequent R01 projects that will explore the potential of miRNA-based therapies for asthma. PUBLIC HEALTH RELEVANCE: Cells that line the airways are important in health and in diseases such as asthma. MicroRNAs are a recently identified class of important regulatory molecules but very little is known about their function in these cells. We will address this knowledge gap to identify new approaches for diagnosing and treating airway diseases.